The regulation of renal blood flow (RBF) depends to a significant extent upon resistance changes in small vessels, particularly arterioles. The response of the preglomerular (afferent) arteriole to certain stimuli is not necessarily identical to that observed in the postglomerular (efferent) arteriole. Further, arteriolar responses in the superficial renal cortex may be quite different from that observed in the juxtamedullary cortex. Control of RBF and renal arteriolar resistance seemingly is mediated largely by those factors which induce autoregulatory adjustments or by a variety of vasoactive mediators, many of which have a renal origin. Among the latter are included the renin-angiotensin and prostaglandin systems and the renal nerves. Certain extrarenal factors, such as circulating catechalomines and arginine vasopressin appear capable of affecting RBF as well. Study of the responses of afferent and efferent arterioles from different levels of the renal cortex in-situ is limited by the inaccessibility of these structures to direct examination and is compromised as it is difficult to examine the singular effect of one experimental variable. The use of techniques which permit study of isolated afferent and efferent arterioles in-vitro provides a means to circumvent these technical difficulties. Such techniques would be ideal in allowing one to compare afferent and efferent arterioles obtained from different levels of the renal cortex. An important aspect of all of the proposed studies is the comparison to be made between the responses seen in afferent and efferent vessels at any level of the cortex and between vessels from the superficial and juxtamedullary renal cortex. In the present proposal, individual afferent and efferent arterioles, obtained from the superficial and juxtamedullary cortex of the dog kidney, will be studied in-vitro. With the use of microperfusion techniques, luminal diameters and intraluminal pressures will be monitored, arteriolar perfusate flow rates measured, and vessel resistances calculated. In the first series of studies, the separate effect of the prostaglandins, PGE2 and PGI2, of angiotensin II, of norepinephrine, and of arginine vasopressin will be studied. In addition, the net effect of the administration of vasoactive mediators in combination, in association with inhibitors of prostaglandin synthesis, or with specific antagonists will be studied. Secondly, the ability of pooled arterioles from each of the four unique anatomic sites to produce PGE2 and PGI2 under basal conditions and after angiotensin II, norepinephrine, and arginine vasopressin is to be determined. Lastly, the autoregulating ability of the four separate arteriolar groups will be examined as the intraluminal pressure is experimentally varied.